Women who took iron supplements during pregnancy had a significantly lower risk of anemia and low-birth-weight babies, according to a large meta-analysis.

Action Points

Note that this meta-analysis of randomized and prospective studies of anemia in pregnancy demonstrates that iron supplementation is associated with improvements in hemoglobin, iron indices, and the risk of low-birth weight.

Be aware that the evidence for iron supplementation reducing the risk of preterm birth was not robust.

Women who took iron supplements during pregnancy had a significantly lower risk of anemia and low-birth-weight babies, according to a large meta-analysis.

Iron supplementation was associated with a 50% reduction in the hazard for anemia and a 19% reduction in the risk of low birth weight.

Supplement use during pregnancy also was associated with a 50% to 60% reduction in the risk of iron deficiency and iron-deficiency anemia. Women who used iron supplements also had a 16% lower risk of preterm birth, but the difference did not achieve statistical significance, Batool A. Haider, of Harvard School of Public Health, and co-authors reported online in BMJ.

Each 10 mg increase in daily iron was associated with a significant increase in birth weight and a significantly lower risk of preterm birth.

Iron deficiency is the most common cause of anemia during pregnancy, accounting for more than half of pregnancy-associated anemia in regions of the world that have fewer alternative causes. Clinical trials have shown that prenatal iron supplementation increases hemoglobin concentration but have not conclusively demonstrated a beneficial effect on birth outcomes, the authors noted in their introduction.

In an effort to clarify the role of supplemental iron during pregnancy, Haider and colleagues performed a meta-analysis of randomized trials to determine the overall effect of iron use on maternal hematologic status, morbidity, and birth outcomes. They performed a separate analysis of large prospective cohort studies to examine the association between prenatal anemia and birth outcomes.

Data for the meta-analyses came from a literature review covering the period from 1966 to May 31, 2012. The authors included randomized trials that evaluated the effect of daily oral iron, with or without folic acid, on maternal hematologic status, morbidity, and birth outcomes.

The analysis of observational studies included prospect cohort studies that assessed the association of baseline maternal anemia with birth outcomes. The authors included studies that defined anemia as hemoglobin <100 g/L or <115 g/L. When hemoglobin was not reported but hematocrit was, investigators estimated hemoglobin from hematocrit values.

The analyses included data from 48 randomized trials involving 17,793 women and 44 cohort studies that included 1,851,682 women. The results showed that iron supplementation was associated with:

4.59 g/L increase in hemoglobin versus control groups

A relative risk of 0.50 for maternal anemia versus control groups

A 41% lower relative risk of iron deficiency

A 60% lower relative risk of iron deficiency anemia

A relative risk of 0.81 for low birth weight

Maternal iron supplementation or fortification was associated with a relative risk of 0.84 for preterm birth, which did not achieve statistical significance (95% CI 0.68-1.03).

The cohort studies showed that anemia in the first or second trimester was associated with a significantly higher risk of low birth weight (OR 1.29, 95% CI 1.09-1.53) and preterm birth (OR 1.21, 95% CI 1.13-1.30).

An exposure-response analysis showed that every 10 mg/d increase in iron (to a maximum of 66 mg/d) was associated with a 12% decrease in the risk of maternal anemia (RR 0.88, 95% CI 0.84-0.92, P<0.001 for linear trend). Additionally each 10 mg increase in daily iron was associated with 15.1-g increase in birth weight (P=0.005) and a 3% decrease in the likelihood of low birth weight (P<0.001).

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